Figure 8.

The hepato‐protective effect of Nutlin‐3a is largely attenuated by downregulation of ApoB. A) 8‐week‐old male C57BL/6J mice were fed CDAHFD for 13 days, followed by intravenous injection with siRNA against ApoB (siApoB) or Stealth siRNA negative control (siNegative) at day 13. The mice were then treated with Nutlin‐3a or vehicle for the remaining experimental period before sacrifice at day 30. B) In vivo TG‐VLDL secretion assay was performed at day 20. The bar chart is fold change of TG‐VLDL secretion rate over the mice treated with siNegative + vehicle (n = 6). C) Serum was collected during TG‐VLDL secretion assay, followed by immunoblotting analysis of ApoB and ApoA‐1. The right panel is densitometric analysis of ApoB100 and ApoB48 normalized with ApoA‐1 (n = 6). D) Hepatic TG contents determined by biochemical assay (n = 4). E,F) Representative images of H&E staining of liver sections. Scale bar: 100 µm. F) NASH score of liver sections in panel E) (n = 6). G) QPCR analysis of genes related to inflammation (upper panel) and fibrosis (lower panel) in livers (n = 5–6). All data are presented as mean ± SEM. n = 6. *p < 0.05, **p < 0.01. (Welch's ANOVA with Dunnett test for panel B); One‐way ANOVA with Tukey test for remaining panels). Not significant (N.S.).